The present invention relates to magnetic resonance imaging and, more particularly, to a method of slice selective multiple quantum magnetic resonance imaging of, for example, connective tissues.
Connective tissues, such as ligaments, tendons and cartilage appear in standard magnetic resonance (MR) images with low signal-to-noise (S/N) ratio (SNR) due to the water short T2 relaxation times. Images performed with short echo time (TE), result in a significant loss of contrast. In addition to the need to enhance the nuclear magnetic resonance (NMR) signal of connective tissues, it is also important to increase the contrast between the different compartments within a specific tissue and between adjacent tissues.
Methods developed to meet these requirements include heavily T, weighted imaging [R. J. Scheck, A. Romagnolo, R. Biemer, T. Pfluger, K. Wilhelm, K. HEran, The carpal ligaments in MR arthrograpby of the wrist: correlation with standard MRI and wrist arthroscopy, J. Magn. Reson. Imag. 1999; 9:468-474] magnetization transfer [T. D. Scholz, R. F. Eyot, J. R. DeLeornardis, T. L. Ceckler, R. S. Balaban, Water-macromolecular proton magnetization transfer in infarcted myocardium: a method to enhance magnetic resonance image contrast, Magn. Reson. Med 1995; 33:178-184; M. L. Gray, D. Burstein, L. M. Lesperance, L. Gehrke, Magnetization transfer in cartilage and its constituent macromolecules, Magn. Reson. Med. 1995; 34: 319-325; R. M. Henkelman, X. Huang, Q.-S. Xiang, G. J. Staniz, S. D. Swanson, M. J. Bronskill, Quantitative interpretation of magnetization transfer, Magn. Reson. Med. 1993; 29:759-766], fat suppression [C. G. Peterfy, S. Majumdar, P. Lang, C. F. van Dijke, K. Sack, H. K. Ganant, MR Imaging of the artitic knee: improved discrimination of cartilage, synovium, and effusion with pulsed saturation transfer and fat-suppressed T1-weighted sequences, Radiology 1994; 191:413-419], diffusion weighted imaging [Y. Xia, T. Farquhar, N. Burton-Wurster, E. Ray, L. Jelinski, Diffusion and relaxation mapping of cartilage-bone plugs and excised disk using micromagnetic resonance imaging, Magn. Reson. Med. 1994; 31:273-282] and projection reconstruction techniques that achieve much shorter echo time than conventional methods [G. E. Gold, J. M. Pauly, A. Macovsky, R. J. Herfkens, MR spectroscopic imaging of collagen: tendons and knee menisci, Magn. Reson. Med. 1995; 34:647-6543].
While these approaches do increase the MR signal of connective tissues and the contrast between connective and adjacent tissues, the results are not yet optimal for diagnostic purposes.
It has recently been demonstrated by the inventors of the present invention that proton double quantum filtered (DQF) NIRI produces a new type of contrast and may serve as a good modality for the imaging of ordered biological tissues [Y. Sharf, Y. Seo, U. Eliav, S. Akselrod, G. Navon, Mapping strain exerted on blood vessel walls using deuterium double quantum filtered MRI, PNAS 1998; 95:4108-4112; L. Tsoref, H. Shinar, G. Navon, Observation of a 1H double quantum filtered signal of water in biological tissues, Magn. Reson. Med. 1998;
39:11-17; Tsoref, H. Shinar, Y. Seo, U. Eliav, G. Navon, Proton Double Quantum Filtered MRIxe2x80x94A New Method for Imaging Ordered Tissues, Magn. Reson. Med. 1998; 40:720-726].
The contrast in DQF MRI stems from the fact that only water molecules associated with ordered structures are detected, and signals originating from molecules in isotropic tissues are suppressed. The 1H DQF signal intensity is sensitive to the magnitude of the residual dipolar interaction and the proton exchange rate between the water molecules [U. Eliav, G. Navon, A study of dipolar interactions and dynamic processes of water molecules in tendon by 1H and 2H homonuclear and heteronuclear multiple-quantum-filtered NMR spectroscopy, J. Magn. Reson. 1999; 137:295-310].
Previous studies of 1H and 23Na multiple quantum imaging [Tsoref, H. 35 Shinar, Y. Seo, U. Eliav, G. Navon, Proton Double Quantum Filtered MRxe2x80x94A New Method for Imaging Ordered Tissues, Magn. Reson. Med. 1998; 40:720-726; M. D. Cockman, L. W. Jelinski, Double-quantum-filtered sodium imaging, J. Magn. Reson. 1990; 90:9-18] did not employ slice selection, and hence were limited to samples that are uniform along one axis.
3-D imaging techniques [R. Kemp-Harper, P. Styles, S. Wimperis, Three-dimensional triple-quantum filtration 23Na NMR imaging, J. Magn. Reson. B. 1995; 108:280-2841] may to some extent solve this problem but are highly time consuming. Thus, for clinical applications a DQF slice selective sequence must be developed.
The short relaxation times of tendons and ligaments poses a particular problem in a straightforward application of slice-selection to the previous DQF MRI pulse sequences [Tsoref, H. Shinar, Y. Seo, U. Eliav, G. Navon, Proton Double Quantum Filtered MRIxe2x80x94A New Method for Imaging Ordered Tissues, Magn. Reson. Med. 1998; 40:720-726].
There is thus a widely recognized need for, and it would be highly advantageous to have, a methods of MR imaging of connective tissue devoid of the above limitations. While reducing the present invention to practice solutions to the above problems were obtained and novel protocols for multiple quantum filtered (MQF) slice selective imaging were developed. It was found that 1H DQF images changed dramatically during the heating process of injured tissues and were more informative than standard MR images. It was further found that although 1H DQF imaging requires high gradient slew-rates, by using composite RF-pulses one can apply 1H multiple quantum techniques with a commercial clinical spectrometer. The quality of the DQF images was evaluated by comparing their SNR and the contrast to noise ratio (CNR) to standard gradient-recalled-echo (GRE) images.
According to the present invention there is provided a method of magnetic resonance imaging of an object, the method comprising the steps of (a) applying a radiofrequency pulse sequence selected so as to select a coherence of an order n to the object, wherein n is zero, a positive or a negative integer other than xc2x11; (b) applying magnetic gradient pulses to the object, so as to select a slice of the object to be imaged and create an image; and (c) acquiring a radiofrequency signal resulting from the object, so as to generate a magnetic resonance slice image of the object.
According to further features in preferred embodiments of the invention described below, the coherence is selected from the group consisting of double quantum filter (DQF), where n equals xc2x12 and triple quantum filter (TQF), where n equals xc2x13.
According to still further features in the described preferred embodiments the coherence is selected by phase cycling or gradient selection.
According to still further features in the described preferred embodiments the radiofrequency is selected so as to enable imaging of an atomic nucleus selected from the group consisting of 1H, 2H and 23Na.
According to still further features in the described preferred embodiments the radiofrequency pulse sequence is selected so as to optimize imaging of the atomic nucleus.
According to still further features in the described preferred embodiments the radiofrequency signal is derived from an atomic nucleus selected from the group consisting of 1H, 2H and 23Na.
According to still further features in the described preferred embodiments a creation time of the radiofrequency pulse sequence is selected so as to maximize the radiofrequency signal or to obtain a desired contrast.
According to still further features in the described preferred embodiments a time to echo as controlled by the magnetic gradient pulses is selected so as to maximize the radiofrequency signal or to obtain a desired contrast.
According to still further features in the described preferred embodiments a repetition time of the radiofrequency pulse sequence is selected sufficiently long so as to minimize single quantum leakage.
According to still further features in the described preferred embodiments the method further comprising the step of (d) applying a crusher pulse prior to step (a) so as to permit shortening of the repetition time.
According to still further features in the described preferred embodiments the crusher pulse is selected from the group consisting of a magnetic gradient pulse, a radiofrequency pulse and a combination thereof.
According to still further features in the described preferred embodiments the crusher pulse includes a first 90xc2x0 radiofrequency pulse, followed by a gradient pulse and a second 90xc2x0 radiofrequency pulse.
According to still father features in the described preferred embodiments a slice refocusing gradient is employed during a time interval selected from the group consisting of a creation time, an evolution time and a time to echo.
According to still filter features in the described preferred embodiments a read gradient is employed during a time interval selected from the group consisting of a creation time, an evolution time and a time to echo.
According to still further features in the described preferred embodiments a phase gradient is employed during a time interval selected from the group consisting of a creation time, an evolution time and a time to echo.
According to still further features in the described preferred embodiments the object is a tissue.
According to still further features in the described preferred embodiments the tissue is a connective tissue.
According to still further features in the described preferred embodiments the tissue is selected from the group consisting of a tendon, a portion of a skin, a bone, a muscle, a cartilage, a blood vessel, a ligament, an organ or a portion thereof, a nerve, a lymph node.
According to still further features in the described preferred embodiments the organ is selected from the group consisting of a brain, a heart, a kidney, a gland, a testicle, an ovary, an eye, a liver, a pancreas and a spleen.
The present invention successfully addresses the shortcomings of the presently known configurations by providing a novel method of slice selective multiple quantum magnetic resonance imaging of connective and other tissues, such as ligaments, tendons and cartilage which appear in standard magnetic resonance images with low signal-to-noise ratio and/or a significant loss of contrast. The novel method, as is further described exemplified hereinbelow overcome the limitations of the standard, prior art, methods.
The invention is herein described, by way of example only, with reference to the accompanying drawings. The file of this patent contains at least one drawing executed in color. Copies of this patent with color drawing(s) will be provided by the Patent and Trademark Office upon request and payment of the necessary fee. With specific reference now to the drawings in detail, it is stressed that the particulars shown are by way of example and for purposes of illustrative discussion of the preferred embodiments of the present invention only, and are presented in the cause of providing what is believed to be the most useful and readily understood description of the principles and conceptual aspects of the invention. In this regard, no attempt is made to show structural details of the invention in more detail than is necessary for a fundamental understanding of the invention, the description taken with the drawings making apparent to those skilled in the art how the several forms of the invention may be embodied in practice.